G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes and detect a wide array of cues in the human body. Here we describe a molecular device ...that couples CRISPR-dCas9 genome regulation to diverse natural and synthetic extracellular signals via GPCRs. We generate alternative architectures for fusing CRISPR to GPCRs utilizing the previously reported design, Tango, and our design, ChaCha. Mathematical modeling suggests that for the CRISPR ChaCha design, multiple dCas9 molecules can be released across the lifetime of a GPCR. The CRISPR ChaCha is dose-dependent, reversible, and can activate multiple endogenous genes simultaneously in response to extracellular ligands. We adopt the design to diverse GPCRs that sense a broad spectrum of ligands, including synthetic compounds, chemokines, mitogens, fatty acids, and hormones. This toolkit of CRISPR-coupled GPCRs provides a modular platform for rewiring diverse ligand sensing to targeted genome regulation for engineering cellular functions.
The uncertainties of a national, bottom-up inventory of Chinese emissions of anthropogenic SO2, NOx, and particulate matter (PM) of different size classes and carbonaceous species are comprehensively ...quantified, for the first time, using Monte Carlo simulation. The inventory is structured by seven dominant sectors: coal-fired electric power, cement, iron and steel, other industry (boiler combustion), other industry (non-combustion processes), transportation, and residential. For each parameter related to emission factors or activity-level calculations, the uncertainties, represented as probability distributions, are either statistically fitted using results of domestic field tests or, when these are lacking, estimated based on foreign or other domestic data. The uncertainties (i.e., 95% confidence intervals around the central estimates) of Chinese emissions of SO2, NOx, total PM, PM10, PM2.5, black carbon (BC), and organic carbon (OC) in 2005 are estimated to be −14%~13%, −13%~37%, −11%~38%, −14%~45%, −17%~54%, −25%~136%, and −40%~121%, respectively. Variations at activity levels (e.g., energy consumption or industrial production) are not the main source of emission uncertainties. Due to narrow classification of source types, large sample sizes, and relatively high data quality, the coal-fired power sector is estimated to have the smallest emission uncertainties for all species except BC and OC. Due to poorer source classifications and a wider range of estimated emission factors, considerable uncertainties of NOx and PM emissions from cement production and boiler combustion in other industries are found. The probability distributions of emission factors for biomass burning, the largest source of BC and OC, are fitted based on very limited domestic field measurements, and special caution should thus be taken interpreting these emission uncertainties. Although Monte Carlo simulation yields narrowed estimates of uncertainties compared to previous bottom-up emission studies, the results are not always consistent with those derived from satellite observations. The results thus represent an incremental research advance; while the analysis provides current estimates of uncertainty to researchers investigating Chinese and global atmospheric transport and chemistry, it also identifies specific needs in data collection and analysis to improve on them. Strengthened quantification of emissions of the included species and other, closely associated ones – notably CO2, generated largely by the same processes and thus subject to many of the same parameter uncertainties – is essential not only for science but for the design of policies to redress critical atmospheric environmental hazards at local, regional, and global scales.
Although modern transportation systems facilitate the daily life of citizens, the ever-increasing energy consumption and air pollution challenge the establishment of green cities. Current studies on ...green IoV generally concentrate on energy management of either battery-enabled RSUs or electric vehicles. However, computing tasks and load balancing among RSUs have not been fully investigated. In order to satisfy heterogeneous requirements of communication, computation and storage in IoVs, this article constructs an energy-efficient scheduling framework for MEC-enabled IoVs to minimize the energy consumption of RSUs under task latency constraints. Specifically, a heuristic algorithm is put forward by jointly considering task scheduling among MEC servers and downlink energy consumption of RSUs. To the best of our knowledge, this is a prior work to focus on the energy consumption control issues of MEC-enabled RSUs. Performance evaluations demonstrate the effectiveness of our framework in terms of energy consumption, latency and task blocking possibility. Finally, this article elaborates some major challenges and open issues toward energy-efficient scheduling in IoVs.
Soil infiltrability, or infiltration capacity, is the rate at which water penetrates into the soil at a rate directly controlled by soil factors alone. The infiltrability is of great importance in ...understanding and managing hydrological processes, crop water supply, irrigation, and soil erosion. The infiltration dynamics measured with the run off-on-out (ROOO) method follows the changes in infiltrability during the infiltration process under rainfall conditions. In this study, the ROOO method was used to quantitatively measure the soil infiltrability under three rainfall intensities (20, 40 and 60
mm/h) and three antecedent soil moisture contents (2.6%, 10.4% and 19.5%, equivalent to 7.5% (air-dry), 30% and 60% of field capacity, respectively, of a clay loam soil. The soil infiltrability determined by the ROOO method decreased with increase in initial soil water content, due to the lower hydraulic gradient at the wetting front. Surface seal formation due to raindrop impact had a significant influence on soil infiltrability and was related to the soil water content. The faster wetting rate of drier soil under higher rainfall intensities, or when using the double-ring infiltrometer for comparison, caused severe aggregate breakdown to promote surface sealing, and significant decrease in soil infiltrability. Cumulative infiltration increased rapidly at the beginning of the infiltration process and then increased approximately linearly with time as the infiltration rate approached to constant. The rate of increase in cumulative infiltration was less under higher initial soil water contents, especially in the initial rainfall stage. Moreover, lower rainfall intensity resulted in higher infiltration rates and greater cumulative infiltration. The soil infiltrability processes measured with the ROOO method were fitted better by Kostiakov, Horton and Philip infiltration models than those measured by the double-ring infiltrometer method. The ROOO method provided reliable data for the entire infiltration process without the limitations of conventional rainfall simulation during the initial phase or of the drawbacks of the double-ring infiltrometer method. The results will have introductory meanings to further studies along this line.
Production of the industrial chemical propylene oxide is energy-intensive and environmentally unfriendly. Catalysts based on bulk silver surfaces with direct propylene epoxidation by molecular oxygen ...have not resolved these problems because of substantial formation of carbon dioxide. We found that unpromoted, size-selected Ag₃ clusters and approximately 3.5-nanometer Ag nanoparticles on alumina supports can catalyze this reaction with only a negligible amount of carbon dioxide formation and with high activity at low temperatures. Density functional calculations show that, relative to extended silver surfaces, oxidized silver trimers are more active and selective for epoxidation because of the open-shell nature of their electronic structure. The results suggest that new architectures based on ultrasmall silver particles may provide highly efficient catalysts for propylene epoxidation.
Measuring the Higgs self-coupling is one of the crucial physics goals at the LHC Run-2 and other future colliders. In this work, we attempt to figure out the size of SUSY effects on the trilinear ...self-coupling of the 125 GeV Higgs boson in the MSSM and NMSSM after the LHC Run-1. Taking account of current experimental constraints, such as the Higgs data, flavor constraints, electroweak precision observables and dark matter detections, we obtain the observations: (1) In the MSSM, the ratio λ3hMSSM/λ3hSM has been tightly constrained by the LHC data, which can be only slightly smaller than 1 and minimally reach 97%; (2) In the NMSSM with λ<0.7, a sizable reduction of λ3h2NMSSM/λ3h2SM can occur and minimally reach 10% when the lightest CP-even Higgs boson mass mh1 is close to the SM-like Higgs boson mh2 due to the large mixing angle between the singlet and doublet Higgs bosons; (3) In the NMSSM with λ>0.7, a large enhancement or reduction −1.1<λ3h1NMSSM/λ3h1SM<2 can occur, which is accompanied by a sizable change of h1τ+τ− coupling. The future colliders, such as the HL-LHC and ILC, will have the capacity to test these large deviations in the NMSSM.
Autophagy is a lysosomal pathway for cellular homeostasis control. Both non-selective bulk autophagy and selective autophagy of specific proteins or organelles have been found. Selective autophagy ...prevents cells from pathogen invasion and stress damage, but its role in regulating transcriptional factors is not clear. Using a macrophage cell differentiation model, the role of autophagy in nuclear factor-κB (NF-κB) regulation is investigated. The bone marrow-derived macrophages (BMDMs) will differentiate into a M2-like phenotype in the presence of hepatoma tumor cell condition medium (CM). The TLR2 signaling drives this M2 polarization and causes NF-κB p65 degradation via lysosome-dependent pathway. The CM-induced ubiquitinated- NF-κB p65 forms aggresome-like structures (ALS) in the cytoplasm of cultured and hepatoma-associated M2 macrophages. This NF-κB p65-contained ALS is recognized by p62/SQSTM1 and degraded by selective autophagy. Treatment with the lysosomal inhibitor bafilomycin A1 or the knockdown of Atg5 can prevent CM-induced NK-κB p65 degradation and induce M2 macrophages to produce a high level of pro-inflammatory cytokines. Furthermore, TLR2 signal induces sustained phosphorylation of extracellular signal-regulated kinase 1/2 to facilitate this autophagy-dependent NF-κB regulation. Our finding provides a novel pathway of NF-κB regulation by p62/SQSTM1-mediated selective autophagy.
Climate change modifies the water and energy fluxes between the atmosphere and the surface in mountainous regions such as the Qinghai-Tibet Plateau (QTP), which has shown substantial hydrological ...changes over the last decades, including rapid lake level variations. The ground across the QTP hosts either permafrost or is seasonally frozen, and, in this environment, the ground thermal regime influences liquid water availability, evaporation and runoff. Consequently, climate-induced changes in the ground thermal regime may contribute to variations in lake levels, but the validity of this hypothesis has yet to be established.
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